sjldllds ;l;sf’;’;s بسم الله الرحمن الرحیم Medical Science University of Isfahan, Anatomical Sciences Department

1390Medical Science University of Isfahan, Anatomical Sciences Department 2 Figure 12.2b من لم یعلم التشریح والنجوم فهو عنّین فی معرفت الله One who do not have the knowledge of Anatomy and Astronomy, will not be able to know God کسی که علم تشریح و نجوم را نداند از شناخت خدا ناتوان ا ست دل هر ذره را که بشکافی آفتابیش در میان بینی

The Limbic System Broca, Papez, Kluver and Bucy Parts of the brain underlying emotional behavior Associated with the olfactory system; rhinencephalon = “smell brain” “The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus, the hippocampus and their interconnections, constitute a harmonious mechanism which may elaborate the functions of central emotion as well as participate in the emotional expression.” - James Papez, Medical Science University of Isfahan, Anatomical Sciences Department

Olfactory System From the Digital Anatomist website thalamus.wustl.edu/ course/lim5.gif Medical Science University of Isfahan, Anatomical Sciences Department

Olfactory Cortex Medical Science University of Isfahan, Anatomical Sciences Department

Medical Science University of Isfahan, Anatomical Sciences Department

Extended amygdala: Central medial group shares continuity and similarity with parts of substantia innominata and bed nucleus of the stria terminalis Connections of the central medial group cal.vet.upenn.edu/neuro/server/ slides/ns_075-BNST.jpg Medical Science University of Isfahan, Anatomical Sciences Department

“C” shaped structure in medial temporal lobe From Digital Anatomist Medical Science University of Isfahan, Anatomical Sciences Department

Development From Digital Anatomist Medical Science University of Isfahan, Anatomical Sciences Department

Gross Anatomy Septal-temporal poles Fornix Fimbria, body, columns Rodent Human Supracommissural hippocampus=supracallosal gyrus, indusium griseum Medical Science University of Isfahan, Anatomical Sciences Department

Connections Afferents: Much of cortex is reciprocally connected to entorhinal cortex Cholinergic and GABA input via septal nuclei Amygdala VTA, LC, Raphe Efferents Via the fornix Precommissural: septal nuclei Post-commisural: mammillary bodies(to anterior thalamic nucleus via mammillothalamic tract) Medical Science University of Isfahan, Anatomical Sciences Department

Medical Science University of Isfahan, Anatomical Sciences Department

Medical Science University of Isfahan, Anatomical Sciences Department

1390Medical Science University of Isfahan, Anatomical Sciences Department 14 THANK YOU

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1390Medical Science University of Isfahan, Anatomical Sciences Department 16 Figure 12.2b Limbic System 18 th Lecture Limbic lobe Hippocampal formatiom Hipocampus

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1390Medical Science University of Isfahan, Anatomical Sciences Department 23 Limbic System Libmbic lobe –Hippocampal formation –Septal area –Parahippocampal gyrus –Cingulate gyrus –Insula Related subcortical nuclei : – Amygdala –Some part of Mesencephalone –Some part of Diencephalone

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1390Medical Science University of Isfahan, Anatomical Sciences Department 26 Limbus = A ring A ring of cortex around Corpus Callosum and Diencephalon

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1390Medical Science University of Isfahan, Anatomical Sciences Department 30 LIMBIC SYSTEM (from

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1390Medical Science University of Isfahan, Anatomical Sciences Department 33 Embryology of Limbic System

1390Medical Science University of Isfahan, Anatomical Sciences Department 34 Embryology of Limbic System

1390Medical Science University of Isfahan, Anatomical Sciences Department 35 Hippocampal formation: 1- Hippocampus, (efferent cortex) 2- Dentate gyrus (afferent cortex) 3- Subiculum (efferent cortex)

1390Medical Science University of Isfahan, Anatomical Sciences Department 36 Cornu Ammonis Hippocampus = Ammon,s horn (Cornu) after Egyptian deity with ram,s head For research purpose, it is divided into 4 cornu ammonis (CA) zones : –CA1 –CA2 –CA3 –CA4

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1390Medical Science University of Isfahan, Anatomical Sciences Department 45 Anatomy of Hippocampus, The hippocampus is a scrolled structure located in the medial temporal lobe. In a coronal section, it looks like a hippocampus

1390Medical Science University of Isfahan, Anatomical Sciences Department 46 Anatomy of Hippocampus

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1390Medical Science University of Isfahan, Anatomical Sciences Department 51 Parts of Hippocampus The hippocampus can be divided into 4 different areas, Areas CA3 and CA1 are more diffuse; the small CA2 is hard to distinguish between them. The dentate gyrus is the dense dark layer of cells at the "tip" of the hippocampus. The subiculum sits at the base of the hippocampus, and is continuous with entorhinal cortex, which is part of the parahippocampal gyrus.

1390Medical Science University of Isfahan, Anatomical Sciences Department 52 Limbic Function Regulate : Emotional and motivational aspects of behavior Limbic projection to forebrain contribute to emotions and provide motivation for behaviors essential to survival

1390Medical Science University of Isfahan, Anatomical Sciences Department 53 Function of limbic System A- Limbic system is able to influence many aspects of emotional behavior via hypothalamus, which in turn employs : –1 Autonomic nervous system –2 Endocrine system B- Converting short term memory to long term memory and facilitate learning

1390Medical Science University of Isfahan, Anatomical Sciences Department 54 Connections of hippocampus 1- Perforant pathway from entorhinal area to dentate gyrus 2- Axons from dentate to pyramidal cell in CA3 sector 3- Axons from CA3 to fimbria 4- A branch from the CA3 fiber called Schaffer collateral, projects to CA1 5- CA1 projects to entorhinal cortex

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1390Medical Science University of Isfahan, Anatomical Sciences Department 56 Afferent Connections to Hippocampus 10 Groups of fibers pass to Hippocampus: 1- Fibers from cingulate gyrus 2- Fibers from septal area 3- Fibers from opposite hippocampus 4- Fibers from indusium grisum 5- Fibers from enthorhinal or olfactory area 6- Fibers from dentate and subiculum

1390Medical Science University of Isfahan, Anatomical Sciences Department 57 Afferents connections cont… 6- From auditory, visual, olfactory association cortex 7- Cholinergic fibers from septal area 8- Noradrenergic fibers from ceruleus nucleus 9- Cerotonergic fibers from raphe nuclei 10- Dopaminergic fibers from ventral tegmental area

1390Medical Science University of Isfahan, Anatomical Sciences Department 58 Efferents from hippocampus 1- Massive effertent fibers to association areas of cortex 2- Fornix fibers to : Septal area Anterior hypothalamus Mammillary body, anterior thalamus and cingulate cortex from which returns to hippocamus Medial forbrain bundle (MFB)

1390Medical Science University of Isfahan, Anatomical Sciences Department 59 Medial forebrain bundle Is a complex group of fibers arising from basal olfactory regions, the septal nuclei, the periamygdaloid region and subiculum that passes to and through, the lateral preoptic and lateral hypothalamic regions. The bundle is formed at the level rostral to the anterior commissure, mainly of fibers from septal regions.

1390Medical Science University of Isfahan, Anatomical Sciences Department 60 Efferent Connections of Hippocampus Axons of large pyramidal cells of hippocampus emerge to form alveus and fimbria and fornix which pass to : 1- Mammillary body 2- Anterior nucleus of thalamus 3- Tegmentum of midbrain 4- Septal area and anterior hypothalamus 5- Habenular nuclei through stria medullaris thalami

1390Medical Science University of Isfahan, Anatomical Sciences Department 61 Papez circuit 1- Backward projection neurons in cingu. G. 2- Projection into entorhinal gyrus 3- Projection into hipp. 4- Fornix 5- Mammillothalamic t 6- Projection from ant. thalamic to cingulate

1390Medical Science University of Isfahan, Anatomical Sciences Department 62 Memory Autopsy and imaging studies of patients with memory disorders suggest that: 1- Hippocampus and related structures, such dorsomedial nucleus of thalamus are important in memory processing. 2- Bilateral damage to these structures results in impairment of recent memory 3- Lesion of hippocampus results in individual being unable to store long term memory 4- Hippocampus is concerned in converting short term memory to long term memory

1390Medical Science University of Isfahan, Anatomical Sciences Department 63 Memory Deficit A stroke can have this effect, but there must be bilateral damage of the hippocampal to affect memory. Therefore only situations that deplete blood or oxygen flow to the entire brain will produce a memory deficit. The pathology of severe temporal lobe epilepsy looks very similar to ischemic damage.

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1390Medical Science University of Isfahan, Anatomical Sciences Department 65 MEMORY If the amygdala is FEAR, then the hippocampus is MEMORY. To understand exactly how the hippocampus is involved in memory, however, you must first know a little about memory.

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1390Medical Science University of Isfahan, Anatomical Sciences Department 68 Diseases of the hippocampus: The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any obstruction of blood flow or oxygen deprivation, Alzheimer's disease, and epilepsy. These diseases selectively attack CA1, which effectively cuts through the hippocampal circuit.

1390Medical Science University of Isfahan, Anatomical Sciences Department 69 Progressive dementia Forgetful, abnormalities of memory, cognition, orientation and behavior Neuronal loss in hippocampus/ parahippocampal gyrus/cortex Reduction in cholinergic innervation of cortex Alzheimer’s Disease

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1390Medical Science University of Isfahan, Anatomical Sciences Department 72 The amygdala If you remember only one word about the amygdala, the word is Fear. And then are: Fight or Flight

1390Medical Science University of Isfahan, Anatomical Sciences Department 73 Inputs to Amygdala The association areas of visual, auditory, and somatosensory cortices are the main inputs to the amygdala It must to recognize the elements of a scene that signal danger.

1390Medical Science University of Isfahan, Anatomical Sciences Department 74 Outputs from Amygdala ِِ Amygdala must be able to control the autonomic system, to provoke such an instant sympathetic response. The main outputs of the amygdala are to the hypothalamus and brainstem autonomic centers, including the vagal nuclei and the sympathetic neurons.

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1390Medical Science University of Isfahan, Anatomical Sciences Department 76 Amygdala The amygdala is also involved with mood and the conscious emotional response to an event, whether positive or negative. To this end, the amygdala is also extensively interconnected with frontal cortex, mediodorsal thalamus, and the medial striatum.

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1390Medical Science University of Isfahan, Anatomical Sciences Department 81 Clinical Points: Kluver-Bucy syndrome following bilateral removal of temporal lobe: 1- Loss of fear and anger 2- Vision agnosia 3- Increased appetite 4- Increased sexual activity

1390Medical Science University of Isfahan, Anatomical Sciences Department 82 Ablation of amygdala suppresses fighting but increases feeding and sexual activity

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1390Medical Science University of Isfahan, Anatomical Sciences Department 84 Reticular formation Phylogenetically a very old neural network Made of nerve fibers and nerve cells Extend through axis of CNS from spinal cord to cerebrum Is strategically placed among nerve tracts and nuclei with vital importance, that is brain stem

1390Medical Science University of Isfahan, Anatomical Sciences Department 85 Neurons of Reticular formation Isodendritic neurons: –Long branching axon –Branching dendrites in a plane vertical to axon

1390Medical Science University of Isfahan, Anatomical Sciences Department 86 Function of Reticular formation It receives input from all sensory systems It gives output to all motor systems

1390Medical Science University of Isfahan, Anatomical Sciences Department 87 General arrangement of reticular formation Reticular formation refers only to polysynaptic network in brain stem although extends cranially and caudally to whole CNS: - Median column, intermediate or raphe nucleus -Medial column, magnocelluar neurons (efferent) -Lateral column, parvicellular neurons, (afferent)

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1390Medical Science University of Isfahan, Anatomical Sciences Department 89 Functions of reticular formation It controls: Skeletal and viscera muscle activity, walking, talking, chewing, laughing, vomiting Somatic and visceral sensations, gating mechanism Autonomic and endocrine system Level of consciousness, reticular activating system Biological clock

1390Medical Science University of Isfahan, Anatomical Sciences Department 90 Components of reticular formation Pattern generators: –Somatic and visceral motor centers –Oscilators Monaminergic group cells which give rise to: –Raphespinal pathway, Serotonergic pathway –Ceruleospinal pathway, noradrenergic pathway

ReticularFormation A. Raphe Nuclei B. Central Nuclear Group Nuclear Group C. Lateral Nuclear Group Nuclear Group D. Precerebellar Reticular Nuclei Reticular Nuclei ABCDABCD Medical Science University of Isfahan, Anatomical Sciences Department

1390Medical Science University of Isfahan, Anatomical Sciences Department 92 THE END